Early-onset Bacterial Infection Research Articles

Procalcitonin-Based Antibiotic Use for Neonatal Early-Onset Bacterial Infections: Pre- and Post-Intervention Clinical Study.

We previously reported the 95th percentile cutoff value of the serum procalcitonin (PCT) reference curve for diagnosing early-onset bacterial infection. We aimed to verify the effectivity of these novel diagnostic criteria by comparing antibiotic use and incidence of early-onset bacterial infection between pre- and post-introduction periods. We included newborns admitted to our neonatal intensive care unit who underwent blood tests within 72 h after birth between 2018 and 2022. The neonates were divided into the pre-intervention (admitted before the introduction, n = 737) or post-intervention (admitted after the introduction, n = 686) group. The days of antibiotics therapy (DOT) per 1000 patient days up to 6 days after birth, percentage of antibiotic use, and incidence of early-onset bacterial infection were compared between the groups. The post-intervention group had significantly lower DOT per 1000 patient days (82.0 days vs. 211.3 days, p < 0.01) and percentage of newborns receiving antibiotics compared with the pre-intervention group (79 (12%) vs. 280 (38%), respectively, p < 0.01). The incidence of early-onset bacterial infections did not differ between the groups (2% each, p = 0.99). In conclusion, our diagnostic criteria using the 95th percentile cutoff value of the serum PCT reference curve for early-onset bacterial infection were proven safe and effective, promoting appropriate use of antibiotics.

Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.

Obstetric Risk Factors and Serological Characteristics of Early-Onset Neonates Bacterial Infections.

PurposeTo analyze the obstetric high-risk factors and serological characteristics of early-onset neonatal bacterial infections (EONBI).Methods119 neonates with early-onset bacterial infection who were admitted to the neonatal ward of our hospital from October 2020 to December 2021 were recorded as the study group, and 100 neonates without bacterial infection who were admitted during the same period were used as the reference group. Comparative analysis of obstetric high-risk factors and serological characteristics of EONBI.ResultsThere was no statistical difference between the two groups in terms of gender and age at admission (P > 0.05). The gestational age and birth weight of newborns in the study group were lower than those in the reference group (P < 0.001). Comparing the maternal factors of EONBI between the two groups, there was no statistical difference in age, number of obstetric inspections, whether to use antibiotics, and mode of delivery (P > 0.05). Univariate analysis showed that preterm birth, unexplained asphyxia, fecal contamination of amniotic fluid, maternal infection during pregnancy, and premature rupture of membranes ≥18 h were significantly associated with EONBI (P < 0.05); while there was no significant difference between the two groups in the comparison between diabetic mother and child and maternal fever at delivery (P > 0.05). Multifactorial analysis showed that preterm birth, fecal contamination of amniotic fluid, maternal infection during pregnancy, and premature rupture of membranes ≥18 h had a good multivariate dependence on EONBI (P < 0.05), while there was no significant association with unexplained asphyxia, diabetic mother and child, and maternal fever at delivery (P > 0.05). The incidence of neonatal temperature >37.9°C was higher in the study group than in the reference group (P < 0.05), and there were no statistical differences in the comparison of other clinical manifestations (P > 0.05). The CRP level of neonates in the study group (47.33 ± 4.14) mg/L was higher than that of the reference group (4.84 ± 1.03) mg/L (P < 0.001). The WBC level of neonates in the study group (5.64 ± 1.18) 109/L was higher than that of the reference group (0.28 ± 0.04) 109/L (P < 0.001). The PCT level of neonates in the study group (5.41 ± 0.85) µg/L was higher than that of the reference group (0.24 ± 0.07) µg/L (P < 0.001).ConclusionEONBI is closely associated with several obstetric high-risk factors, including preterm birth, fecal contamination of amniotic fluid, maternal infection during pregnancy, and premature rupture of membranes ≥18 h; EONBI has no specific symptoms and signs, but serum CRP, WBC, and PCT levels are significantly higher than those of newborns without co-infection with bacteria.

The Predictive Value of Procalcitonin and High-Sensitivity C-Reactive Protein for Early Bacterial Infections in Preterm Neonates

Introduction: Evidence on the reliability of using procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) as diagnostic markers for early-onset neonatal bacterial infections is still insufficient because of their physiological elevation during the early neonatal period. This study aimed to assess the respiratory influence of serum PCT and hs-CRP levels and evaluate their predictive value for bacterial infections during the first 72 h of life in preterm neonates. Methods: The preterm neonates enrolled in this single-center retrospective cohort study were categorized into 3 groups: reference, infection-unlikely respiratory failure, and probable bacterial infection; their serum PCT and hs-CRP levels were assessed. Subsequently, age-specific 95th percentile curves were plotted and the median and cutoff PCT and hs-CRP levels for predicting bacterial infections at birth and 7–18, 19–36, and 37–72 h after birth were determined. Moreover, the analysis of PCT and hs-CRP with a neonatal sequential organ failure assessment (nSOFA) score was performed in very low birth weight neonates. Results: Serum PCT levels were influenced by respiratory failure. A significant difference was found in the median PCT and hs-CRP levels among the 3 groups at each time point. PCT sensitivities for predicting bacterial infection were slightly higher than those of hs-CRP in each time frame during the first 72 h of life. In both PCT and hs-CRP, there was no significant difference between infants with nSOFA scores of >4 and those with nSOFA scores of ≤4. Discussion/Conclusion: Age-specific evaluation showed that PCT has better predictive value than hs-CRP for early-onset bacterial infections in preterm neonates.

DEVELOPMENT OF ARTERIAL HYPOTENSION IN PREMATURE INFANTS WITH EARLY ONSET BACTERIAL INFECTIONS: TOOLS OF CLINICAL PREDICATION

Introduction: The safe thresholds of blood pressure in preterm neonates are still unclear. The aim of our study was to substantiate the diagnostic criteria for the syndrome of arterial hypotension (AH) and indications for the appointment of hemodynamic support in premature infants with early onset bacterial infections. Materials and methods: A prospective cohort study was conducted. 2 experimental groups were formed -premature babies with early onset bacterial infections and AH (n = 58), and control group (n = 62), premature babies without AH. The subjects of the study were a number of risk factors. Simple and multiple logistic regression analyses were used. Results: In premature infants with AH, compared with those without AH, there are significantly lower values of stroke index of left ventricle (SILV), index of resistance (IR) of the middle cerebral artery, pH, significantly higher level of urea in serum and a higher proportion of children with hypoglycemia. Multiple logistic regression analysis was used to develop a clinical prognostic model for the AH-syndrome. Only prognostic model, which included SILV, blood pH and blood glucose, had high prognostic characteristics and the largest area under the ROC curve. Conclusions: The following diagnostic criteria can be used for the appointment of medical support for hemodynamics: the digital value of the level of mean blood pressure, expressed in mmHg, is less than the gestational age in weeks, and at least one of the following indicators -pH is less than 7.2, blood glucose level is less than 2.8 mmol/l, SILV is less than the normal ranges.

Epidemiology of Early-onset Bacterial Neonatal Infections in Madagascar.

Little is known about early-onset neonatal bacterial infections (EONBI) in Madagascar. Our aim was to determine their epidemiology to improve their management. Inborn neonates at risk for EONBI and admitted in the neonatal unit of 2 tertiary hospitals in Antananarivo, Madagascar, were included in a prospective study from April 2012 to March 2013. Using a clinical algorithm, blood culture, gastric fluid culture and C-reactive protein dosage were performed in newborns at high risk of infection, that is, peri partum fever, prematurity <35 weeks' gestation or birth weight <2000 g, or presenting with clinical signs of infection. EONBI was defined as a bacteremia occurring within the first week of life. Among 307 neonates, 75 (24.4%) had an EONBI caused by 1 (n = 59) or 2 (n = 16) bacteria (91 isolates). Gram-negative bacteria were predominant (n = 62, 82.7%), including Enterobacter cloacae (n = 26), Klebsiella pneumoniae (n = 14), Escherichia coli (n = 7) and Proteus mirabilis (n = 2). Group B Streptococcus, Acinetobacter baumanii and Enterococcus sp. represented 3.6%, 8.2% and 12.1% of the isolates, respectively. All E. cloacae and 12/14 (85.7%) K. pneumoniae were extended-spectrum β-lactamase producers. At all, 41/91 (45.1%) bacteria were multidrug-resistant (MDR) and 34/75 (45.3%) newborns had an EONBI caused by an MDR bacteria. Neonatal asphyxia was the only factor associated with multidrug resistance (odds ratio: 4.52; CI: 1.20-16.94; P = 0.025). The EONBI-related mortality (n = 20/75, 26.7%) rose up to 38.2% (n = 13/34) in case of MDR bacteria. The epidemiology of EONBIs in Madagascar is comparable to that found in many low-income countries. Prevention, including improvement of hygiene during resuscitation for neonatal asphyxia, is likely to be more effective in reducing EONBI-related morbidity and mortality than using new antibiotics to counter resistance.

Novel HAX1 Gene Mutation in a Vietnamese Boy with Severe Congenital Neutropenia

Severe congenital neutropenia (SCN) is a rare disease that involves a heterogeneous group of hereditary diseases. Mutations in the HAX1 gene can cause an autosomal recessive form of SCN-characterized low blood neutrophil count from birth, increased susceptibility to recurrent and life-threatening infections, and preleukemia predisposition. A 7-year-old boy was admitted due to life-threatening infections, mental retardation, and severe neutropenia. He had early-onset bacterial infections, and his serial complete blood count showed persistent severe neutropenia. One older sister and one older brother of the patient died at the age of 6 months and 5 months, respectively, because of severe infection. Bone marrow analysis revealed a maturation arrest at the promyelocyte/myelocyte stage with few mature neutrophils. In direct DNA sequencing analysis, we found a novel homozygous frameshift mutation (c.423_424insG, p.Gly143fs) in the HAX1 gene, confirming the diagnosis of SCN. The patient was successfully treated with granulocyte colony-stimulating factor (G-CSF) and antibiotics. A child with early-onset recurrent infections and neutropenia should be considered to be affected with SCN. Genetic analysis is useful to confirm diagnosis. Timely diagnosis and suitable treatment with G-CSF and antibiotics are important to prevent further complication.

Clinical presentation, immunologic features, and hematopoietic stem cell transplant outcomes for IKBKB immune deficiency

IKBKB immune deficiency is a rare but life-threatening primary immunodeficiency disorder, involving activation defects in adaptive and innate immunity. We present sixteen cases of a homozygous IKBKB mutation (c.1292dupG) in infants characterized by early-onset bacterial, viral, fungal and Mycobacterial infections. In most cases, T- and B-cells were quantitatively normal, but phenotypically naïve, with severe hypogammaglobulinemia. T-cell receptor excision circles were normal, meaning newborn screening by TREC analysis would miss IKBKB cases. Although IKBKB immune deficiency does not meet traditional laboratory based definitions for SCID, this combined immune deficiency appears to be at least as profound. Urgent HSCT, performed in eight patients, remains the only known curative therapy, although only three patients are survivors. Ongoing infections after transplant remain a concern, and may be due to combinations of poor social determinants of health, secondary graft failure, and failure of HSCT to replace non-hematopoietic cells important in immune function and dependent upon IKK/NF-κB pathways.

Infection néonatale bactérienne précoce (INBP) : quel algorithme de prise en charge en 2017 ?

In the era of intrapartum chemoprophylaxis to reduce GBS, rates of early onset bacterial infection have declined in term newborns. New guidelines have been written in order to adapt our current practices to this epidemiological evolution and limit excessive exams and antibiotic administrations. The main point of these new guidelines consists in a clinical systematic surveillance in maternity for well appearing newborns instead of the current empiric antibiotic treatment. Advised biological exams are also detailed.

Low Rate of Perinatal Sepsis in Term Infants of Mothers with Chorioamnionitis.

The risk of infection in infants of mothers with chorioamnionitis (CAM) may be lower than previously reported. This study's objective was to determine the incidence of intrapartum fever (IPF) and culture-positive early-onset bacterial neonatal infection (CPEOI) in the late preterm and term infants of mothers with or without CAM and to assess interhospital variation in neonatal infection management. This retrospective cohort study included mothers and newborns delivered at ≥35 weeks gestation at Kaiser Permanente Southern California Hospitals in 2010 (n = 31,112). Electronic medical and laboratory records from 13 medical centers were examined for maternal temperature, intrapartum, and neonatal antibiotic treatment. Rates for IPF, CAM, and CPEOI were estimated. Rates for starting neonatal antibiotics were calculated. The incidence of IPF was 9% and CAM 4%. The overall rate for CPEOI was 0.61/1,000 (95% confidence interval [CI] 0.34, 0.89/1,000). The rate of CPEOI was 4.0/1,000 (95% CI 0.50, 7.5/1,000) in infants born to mothers with CAM. The rate of beginning antibiotics for infants born to mothers with CAM ranged from 7 to 76% between nurseries. The rate of CPEOI in infants born to mothers with CAM is lower than previously reported. There is heterogeneity in initiation of neonatal antibiotics by neonatologists.

Diagnostic value of immature myeloid information in early-onset bacterial infection in term and preterm neonates.

For quick detection of neonatal early-onset bacterial infection (EOBI) pro-inflammatory cytokines like Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in combiantion with C-reactive Protein (CRP) have been used. Automated determination of immature myeloid information (IMI) seems to be an additional useful tool in the diagnosis of NBI. To compare the diagnostic value of IMI, I/T-Ratio, plasma IL-6 and IL-8 levels and CRP in term and preterm neonates at time of clinical suspicion of EOBI. 31 preterm and 123 term neonates with clinical and serological signs of EOBI were analysed. 91 preterm and 159 term neonates with risk factors but without proven EOBI served as non-infected controls. Neonates with EOBI showed significantly elevated IMI levels at time of first clinical suspicion of EOBI (Preterm: 1 028/µL (38-8 759) vs. 289/µL (6-3 126); Term: 1 268/µL (48-14 035) vs. 856/µL (19-5 735); p<0.05 respectively). I/T-Ratio, IL-6, IL-8 and CRP values were significantly higher in preterm and term neonates with EOBI (p<0.05). Sensitivity of IMI at a cut-off level of 650/µL was 84.2% [95%-CI: 74.0-91.6%] in preterm and 65.4% [95%-CI: 56.8-73.3%] in term infants. Specificity was 66.7% [95%-CI: 47.1-82.7%] and 53.9% [95%-CI: 43.8-63.7%], respectively. Combination of different infection parameters improved sensitivity up to 93.5% and specificity up to 98.9%. The diagnostic value of IMI in diagnosing EOBI in preterm and term neonates is not comparable to IL-6, IL-8 and CRP. Combination of IMI-Channel with IL-6, IL-8 or CRP improves their sensitivity, specificity and predictive value.

Diagnostic Value of an Interleukin-6 Bedside Test in Term and Preterm Neonates at the Time of Clinical Suspicion of Early- and Late-Onset Bacterial Infection

Background: For quick detection or exclusion of neonatal early-onset bacterial infection (EOBI) or late-onset bacterial infection (LOBI), interleukin (IL)-6 is used. Its clinical use is sometimes limited due to prolonged recall times. Therefore, an IL-6 bedside test was established. Objective: To compare the diagnostic value of plasma IL-6 and an IL-6 bedside test at the time of clinical suspicion in the course of EOBI and LOBI. Methods: Eighteen term (mean gestational age 40.2 weeks, SD 1.3) and 88 preterm (mean gestational age 30.1 weeks, SD 4.2) neonates with clinical and serological signs of bacterial infection were analysed. Eight had an EOBI, and 24 had a LOBI, of whom 13 were blood culture positive. Twelve term and 62 preterm neonates with risk factors but without proven EOBI/LOBI served as a non-infected group. Results: At the time of clinical suspicion, the sensitivity of the IL-6 bedside test in comparison to plasma IL-6 was 69 versus 75% (p = 0.7744, McNemar’s test), and specificity was 77 versus 81% (p = 0.6476, McNemar’s test; cutoff level 50 ng/l). For LOBI, both the sensitivity (75%) and specificity (82%) of the bedside test exceeded values calculated for EOBI (sensitivity 50%, specificity 75%). Conclusion: No significant difference between the bedside and established plasma IL-6 test was detected for LOBI. For detection of EOBI, the bedside test was not sensitive enough. Larger studies are needed to verify our findings before IL-6 bedside tests can be recommended routinely.

Estimating the Probability of Neonatal Early-Onset Infection on the Basis of Maternal Risk Factors

To develop a quantitative model to estimate the probability of neonatal early-onset bacterial infection on the basis of maternal intrapartum risk factors. This was a nested case-control study of infants born at ≥34 weeks' gestation at 14 California and Massachusetts hospitals from 1993 to 2007. Case-subjects had culture-confirmed bacterial infection at <72 hours; controls were randomly selected, frequency-matched 3:1 according to year and birth hospital. We performed multivariate analyses and split validation to define a predictive model based only on information available in the immediate perinatal period. We identified 350 case-subjects from a cohort of 608,014 live births. Highest intrapartum maternal temperature revealed a linear relationship with risk of infection below 100.5°F, above which the risk rose rapidly. Duration of rupture of membranes revealed a steadily increasing relationship with infection risk. Increased risk was associated with both late-preterm and postterm delivery. Risk associated with maternal group B Streptococcus colonization is diminished in the era of group B Streptococcus prophylaxis. Any form of intrapartum antibiotic given >4 hours before delivery was associated with decreased risk. Our model showed good discrimination and calibration (c statistic = 0.800 and Hosmer-Lemeshow P = .142 in the entire data set). A predictive model based on information available in the immediate perinatal period performs better than algorithms based on risk-factor threshold values. This model establishes a prior probability for newborn sepsis, which could be combined with neonatal physical examination and laboratory values to establish a posterior probability to guide treatment decisions.

Influence of Gestational Age, Cesarean Section and Hematocrit on IL-8 Concentrations in Plasma and Detergent-Lysed Whole Blood of Noninfected Newborns

Background: Sensitivity of interleukin-8 (IL-8) in detecting early-onset bacterial infection (EOBI) is high. A high percentage is bound to nonspecific receptors on erythrocytes which can be determined via cell lysis. We have shown detergent-lysed whole blood (DLWB) IL-8 to be superior to plasma IL-8 in detecting EOBI. Methods: To evaluate influence of pre- and perinatal factors on plasma and DLWB IL-8 concentrations, IL-8 was determined via ELISA (Immulite) in 146 noninfected newborns with risk factors for EOBI at two different time periods: 0–6 (group I) and 24–30 h (group II) after birth. The influence of gender, mode of delivery, gestational age and hematocrit was evaluated. Results: While we found no influence of gender or gestational age, hematocrit was positively correlated with IL-8 plasma concentration (group I: r = 0.33, p < 0.001; group II: r = 0.30, p <0.01). IL-8 plasma concentrations after primary versus secondary cesarean section were lower (p < 0.05). Gestational age was correlated with DLWB IL-8 concentrations (group I: r = 0.46, p < 0.001; group II: r = 0.28, p < 0.001). Conclusion: Plasma IL-8 concentrations were positively correlated with hematocrit, whereas DLWB IL-8 concentrations increased with gestational age. This may be relevant to the interpretation of IL-8 in preterm infants and infants with anemia, polyglobulia or hematolytic diseases.

Diagnostic value of interleukin-6 and C-reactive protein on early onset bacterial infection in preterm neonates with respiratory distress

To evaluate the C-reactive protein (CRP) and interleukin-6 (IL-6) as diagnostic tools for early onset infection in preterm infants with early respiratory distress (RD). CRP and IL-6 were quantified at identification of RD and 24 h after in 186 newborns. Effects of maternal hypertension, mode of delivery, Apgar score, birth weight, gestational age, mechanical ventilation, being small for gestational age (SGA), and the presence of infection were analyzed. Forty-four infants were classified as infected, 42 as possibly infected, and 100 as uninfected. Serum levels of IL-6 (0 h), CRP (0 h), and CRP (24 h), but not IL-6 (24 h) were significantly higher in infected infants compared to the remaining groups. The best test for identification of infection was the combination of IL-6 (0 h) 36 pg/dL and/or CRP (24 h) 0.6 mg/dL, which yielded 93% sensitivity and 37% specificity. The presence of infection and vaginal delivery independently increased IL-6 (0 h), CRP (0 h) and CRP (24 h) levels. Being SGA also increased the CRP (24 h) levels. IL-6 (24 h) was independently increased by mechanical ventilation. The combination of IL-6 (0 h) and/or CRP (24 h) is helpful for excluding early onset infection in preterm infants with RD but the poor specificity limits its potential benefit as a diagnostic tool.

Plasma lipopolysaccharide-binding protein levels in neonatal early-onset bacterial infection

Plasma lipopolysaccharide-binding protein levels in neonatal early-onset bacterial infection

Delayed-Onset Primary Cytomegalovirus Disease and the Risk of Allograft Failure and Mortality after Kidney Transplantation

During the contemporary era of antiviral prophylaxis, the impact of delayed-onset primary cytomegalovirus (CMV) disease on the outcome of kidney transplantation is not known. We evaluated the incidence, clinical features, risk factors, and outcomes of CMV disease among high-risk kidney transplant recipients. The medical records of CMV-seronegative recipients of kidney transplants from CMV-seropositive donors were reviewed. Cox proportional hazards regression was used to identify factors associated with CMV disease and to assess its impact on allograft loss and mortality. None of the 176 CMV-seronegative recipients of kidney transplants from CMV-seropositive donors developed breakthrough CMV disease during a median of 92 days (interquartile range, 90-92 days) of oral ganciclovir or valganciclovir prophylaxis. Thereafter, 51 patients (29%) developed CMV disease at a median of 61 days (interquartile range, 40-143 days) after stopping antiviral prophylaxis. Early-onset bacterial and fungal infection (hazard ratio, 3.61; 95% confidence interval, 1.78-7.33; p < .001) and a Charlson comorbidity index > or =3 (hazard ratio, 2.21; 95% confidence interval, 1.15-4.22; p = .011) were associated with a higher risk of delayed-onset primary CMV disease, and postrejection antiviral prophylaxis (hazard ratio, 0.29; 95% confidence interval, 0.09-0.94; P = .039) was associated with a lower risk of such CMV disease. A time-dependent Cox regression analysis revealed a statistically significant association between tissue-invasive CMV disease and allograft loss or mortality (hazard ratio, 2.85; 95% confidence interval, 1.22-6.67; P = .016). This study of a large cohort of CMV-seronegative recipients of kidney transplants from CMV-seropositive donors illustrates the ongoing challenge of delayed-onset primary CMV disease and its impact on transplantation outcomes despite antiviral prophylaxis. Better strategies for CMV disease prevention after kidney transplantation are warranted.

C-Reactive Protein, Detected with a Highly Sensitive Assay, in Non-Infected Newborns and Those with Early Onset Infection

Backgound: The aim of this study was to investigateC-reactive protein (CRP), measured by a highly sensitivemethod (hsCRP) in non-infected newborns and in thosewith suspected early onset bacterial infection (EOBI) aswell as to test whether EOBI would be detectable earlierby hsCRP than by a nephelometric CRP (nsCRP) assay(thresholds > 10 mg/l) or IL-8. Patients and Methods: 106neonates with signs of infection comprised the suspectedEOBI group. 134 neonates with risk factors but confirmedexclusion of EOBI served as non-infected controls.Results: In the non-infected group, hsCRP in thefirst 6 h after birth was low (0.7 mg/l; SD 0.16 mg/l) butshowed an increase to 4.11 mg/l (SD 3.33 mg/l) at 72 h(p < 0.001 vs. 6 h). The sensitivity of hsCRP (cut-off0.3 mg/l) vs. nsCRP for EOBI was 0.46 vs. 0.23 at 6 h afterclinical suspicion. Of all parameters measured, IL-8 hadthe highest sensitivity and specificity to detect EOBI at6 h (0.60 and 0.90), but declined after 12 and 24 h. Conclusion:Lowering the CRP detection threshold by a highlysensitive assay did not improve diagnostic accuracyfor EOBI.

Characteristics of Inflammatory Bowel Disease With Onset During the First Year of Life

Inflammatory bowel disease (IBD) is recognized in young children, however, only rare data on onset and evolution are available in children younger than 1 year. In the present clinical study, we aimed to analyze characteristics and clinical course of children with very early onset IBD. We were particularly interested in the relationship between bacterial infections and the use of antibiotics before the onset of IBD. The IBD database of Necker-Enfants-Malades-Hospital was screened for patients with IBD with disease onset during the first year of life and a follow-up of at least 2.5 years. Ten patients were identified during the period 1996-2002. All patients presented with rectal bleeding and had colonic involvement. Four patients had definitive diagnosis of Crohn disease; ulcerative or indeterminate colitis was seen in 2 and 4 children, respectively. Five of the patients had a positive history of neonatal or early-onset bacterial infection with use of antibiotics before onset of IBD, 4 patients were still breastfed and 3 just weaned when GI symptoms started. Seven patients had a severe onset of disease requiring bowel rest, parenteral nutrition and steroid medication, followed by azathioprine or cyclosporine medication. Surgery was necessary in 3 of 10 patients. Disease relapses were frequent and observed in 8 of 10 children. Very early onset IBD may reflect a subgroup of patients characterized by a particular sensitivity to modifications of the intestinal flora. Neonatal IBD was most often severe in presentation and evolution.

Low blood neutrophil concentrations among extremely low birth weight neonates: data from a multihospital health-care system

A blood neutrophil concentration < 1000/microl has been reported to occur in about 8% of neonatal intensive care unit (NICU) patients, at some time during their hospital stay. However, the incidence of this finding among extremely low birth weight (ELBW) neonates (< 1000 g birth weight) is not known. Using data from four NICU's in one health-care system, we sought to estimate the incidence, timing, causes, severity and duration of neutrophil counts < 1000/microl among ELBW neonates. We also tabulated the treatments used for this condition and associations with mortality. We performed an historic cohort analysis of all ELBW neonates born during the 36-month period, 1 July 2002 to 30 June 2005, cared for in the four Intermountain Healthcare level III NICU's. Three hundred and thirty-eight ELBW neonates were the subjects of the analysis. Complete blood cell counts (CBCs) were obtained in all (range, 1 to 123 CBCs/patient). Thirty-eight percent (128/338) had one or more neutrophil counts < 1000/microl. In 57% the low neutrophil count persisted for < 24 h; in 43% it persisted for 1 to 7.5 days. Most of the cases (74%) were detected during the first 3 days of life. Twenty-two percent of cases were not detected until after the first week. Low neutrophil counts were more common among the smallest patients, with a 63% incidence in those < or = 500 g, 44% in those 501 to 600 g and 34% in those 801 to 999 g. When low neutrophil counts were recognized during the first 3 days of life, the patients were typically either small for gestational age (SGA; weight < 10th percentile for gestational age) or born after pregnancy-induced hypertension (PIH) (68%), or had early-onset bacterial infection (6%). When recognized after the first 3 days, the patients typically had necrotizing enterocolitis (31%) or a nosocomial bacterial infection (19%). Alloimmune mechanisms were not tested for in any of the cases. No cause for the low counts was identified among 35% of the neutropenic patients. Intravenous immunoglobulins was administered to 28% of cases, and 100% of these were given according to our written guidelines. Recombinant granulocyte-colony stimulating factor was administered to 13% of cases, and 69% of these were given according to guidelines. Neither the presence of low neutrophil counts nor the severity (lowest recorded count) correlated with mortality rate, except in proven early-onset sepsis. We observed low neutrophil counts among ELBW neonates at a rate five times that reported in the general NICU population. Most cases were present in the first days of life and occurred in SGA neonates or those with PIH. In over 1/3, no cause was discovered. We maintain that more consistency is needed in evaluating and treating neutropenia among ELBW neonates.